rs907141

Variant names:

• chr2-219564524-C-G
• rs907141
• NM_015311.3:c.2407+718G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015311.3(OBSL1):​c.2407+718G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,192 control chromosomes in the GnomAD database, including 25,813 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (25813 hom., cov: 34)
• Consequence: OBSL1 NM_015311.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 3 publications found

Genes affected

OBSL1 (HGNC:29092): (obscurin like cytoskeletal adaptor 1) Cytoskeletal adaptor proteins function in linking the internal cytoskeleton of cells to the cell membrane. This gene encodes a cytoskeletal adaptor protein, which is a member of the Unc-89/obscurin family. The protein contains multiple N- and C-terminal immunoglobulin (Ig)-like domains and a central fibronectin type 3 domain. Mutations in this gene cause 3M syndrome type 2. Alternatively spliced transcript variants encoding different isoforms have been found in this gene. [provided by RefSeq, Mar 2010]

OBSL1 Gene-Disease associations (from GenCC):

• 3M syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• 3-M syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015311.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBSL1	NM_015311.3	MANE Select	c.2407+718G>C		intron	N/A	NP_056126.1
	OBSL1	NM_001173431.2		c.2407+718G>C		intron	N/A	NP_001166902.1
	OBSL1	NM_001173408.2		c.2407+718G>C		intron	N/A	NP_001166879.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBSL1	ENST00000404537.6	TSL:1 MANE Select	c.2407+718G>C		intron	N/A	ENSP00000385636.1
	OBSL1	ENST00000373873.8	TSL:1	c.2407+718G>C		intron	N/A	ENSP00000362980.4
	OBSL1	ENST00000373876.5	TSL:5	c.2407+718G>C		intron	N/A	ENSP00000362983.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84969 AN: 152074 Hom.: 25794 Cov.: 34

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.596

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.559 AC: 85023 AN: 152192 Hom.: 25813 Cov.: 34 AF XY: 0.563 AC XY: 41904 AN XY: 74408

African (AFR) AF: 0.303 AC: 12563 AN: 41508

American (AMR) AF: 0.536 AC: 8204 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2205 AN: 3470

East Asian (EAS) AF: 0.672 AC: 3477 AN: 5176

South Asian (SAS) AF: 0.729 AC: 3522 AN: 4830

European-Finnish (FIN) AF: 0.706 AC: 7486 AN: 10598

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45508 AN: 67990

Other (OTH) AF: 0.599 AC: 1266 AN: 2114

Alfa AF: 0.615 Hom.: 3777

Bravo AF: 0.531

Asia WGS AF: 0.686 AC: 2387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.73
PhyloP100		0.032
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs907141; hg19: chr2-220429246;